Congenital anomalies are the second leading cause of perinatal mortality in the United States after premature birth. Advances in imaging techniques have allowed the in utero detection of many anatomical defects with ultrasound. The goal of this project is to improve the diagnosis and treatment of fetal disease and congenital anomalies. The Perinatology Research Branch has initiated a series of projects to improve the detection of congenital anomalies as well as assess fetal growth and development with the use of three-dimensional ultrasound. A substantial effort has been invested in the development of techniques to improve the prenatal diagnosis of congenital heart disease, since this is the leading cause of death among fetuses with congenital anomalies. We have also explored the diagnostic potential of novel technological developments that allow real-time three-dimensional scanning of the fetus using two-dimensional matrix array transducers. The findings of this year include the following:[unreadable] [unreadable] 1. Tomographic ultrasound imaging for the examination of the fetal heart. A recent technological development allows automatic slicing of volume datasets acquired using three-dimensional or four-dimensional ultrasonographic techniques in either the transverse, sagittal or coronal planes. A series of slices resembling the display commonly utilized to read computerized tomography or magnetic resonance is obtained by this method. Investigators at the Perinatology Research Branch sought to determine the feasibility of conducting a comprehensive echocardiographic examination in fetuses with and without congenital heart disease. Using the automated tomographic slicing of the fetal heart, standard views such as the four-chamber view, five-chamber view as well as three-vessel and trachea view were visualized in 97.4%, 88.2% and 79.5% of the cases, respectively. The addition of color Doppler allowed visualization of these planes in 98.2%, 97.0%, and 83.6% of the cases, respectively.[unreadable] [unreadable] 2. A novel algorithm for comprehensive fetal echocardiography using four-dimensional ultrasonography and tomographic imaging. This study explored the possibility of combining tomographic ultrasound imaging with a pre-defined set of manipulations of the volume dataset to systematically visualize the four-chamber view, the long axis view of the aorta, the short axis view of the pulmonary artery, and the three vessel and trachea view in a single image divided in four frames. The objectives of this novel algorithm are to both facilitate the performance of a thorough fetal echocardiographic examination from a single volume dataset of the fetal heart, and allow documentation of the essential planes of section in a single image to facilitate comparison. Using the proposed algorithm, simultaneous visualization of the short axis of the pulmonary artery, the three-vessel and trachea view, the left outflow tract, as well as the four-chamber view of the heart was possible in 78% of the fetuses with no congenital heart disease, and in 40% of those with congenital heart disease.[unreadable] [unreadable] 3. What does two-dimensional imaging add to three- and four-dimensional obstetric ultrasonography? When three-dimensional ultrasound is performed using mechanical probes, the volume dataset is generated by assembling a series of two-dimensional images obtained automatically by the probe, with precise spatial orientation. Three-dimensional volume datasets can then be sliced and displayed in any desired plane of section and should contain the same or more information than that provided by the original two-dimensional images. This principle has been recently explored by some investigators who have proposed that the examination of volume datasets alone could be used to streamline ultrasound examinations in busy clinical practices. A crucial question is whether the information contained in the volume dataset can be trusted. Investigators of the Perinatology Research Branch conducted a blinded study comparing the diagnostic information provided by examination of volume datasets alone against those obtained during a conventional two-dimensional ultrasonographic examination. The same examiner, who was blinded to the indications for the examination, evaluated the three-dimensional volume datasets first, established a diagnostic impression, and then conducted a two-dimensional ultrasound examination. This approach is innovative, as two-dimensional ultrasonography was performed first in previous studies comparing two-dimensional versus three-dimensional ultrasonography. Agreement between three-dimensional and the two-dimensional ultrasound was observed for 90.4% of the findings, with no difference in sensitivity and specificity for the diagnosis of congenital anomalies between the two methods. Artifacts related to fetal motion during acquisition led to an erroneous diagnosis of double-outlet right ventricle instead of transposition of the great arteries in one case.[unreadable] [unreadable] 4. Applications of two-dimensional matrix array for three- and four-dimensional examination of the fetus. Investigators at the Perinatology Research Branch also explored the potential applications of two-dimensional matrix array technology for the examination of fetal structures other than the fetal heart. Two-dimensional matrix array is a new technology that was originally developed for the examination of adult hearts by real-time three-dimensional echocardiography. The advantage of this technology is that it does not require reconstruction of two-dimensional images to form the volume dataset and, therefore, temporal resolution is optimal. Our preliminary experience with this technology indicates that it allows 360 degree rotation of fetal structures in real-time, without the need to move the transducer. This facilitates the examination of structures from multiple angles, with the potential of facilitating the diagnosis of congenital anomalies. Limitations with currently available technology were identified and were related to lower resolution and narrower volume display compared to conventional three-dimensional volumetric techniques.